Sponsoring Section/Society: ASA-BIOPHARM
Session Slot: 10:30-12:20 Monday
Estimated Audience Size: 200-250
AudioVisual Request: Two Overheads
Theme Session: Yes
Applied Session: Yes
Session Title: Assessment of the U.S. FDA Draft Guidance on Statistical
Procedures for Bioequivalence Studies
Session Organizer: Liu, Jen-pei National Cheng-kung University
Address: Department of Statistics National Cheng-kung University Tainan, Taiwan 70101
Phone: 886-6-275-7575 ext 53622
Fax: 886-5-234-2469
Email: jpliu@hpstat.ncku.edu.tw
Session Timing: 110 minutes total (Sorry about format):
Opening Remarks by Chair - 5 minutes First Speaker - 25 minutes Second Speaker - 25 minutes Third Speaker - 25 minutes Discussant - 15 minutes Floor Discussion - 15 minutes
Session Chair: Liu, Jen-pei National Cheng-kung University
Address: Department of Statistics National Cheng-kung University Tainan, Taiwan 70101
Phone: 886-6-275-7575 ext 53622
Fax: 886-5-234-2469
Email: jpliu@hpstat.ncku.edu.tw
1. Population and Individual Bioequivalence: A View from the Pharmaceutical Science Advisory Committee
Davidian, Marie, North Carolina State University
Address: Department of Statistics Box 8203 North Carolina State Univ. Raleigh NC 27695-8203
Phone: 919-515-1940
Fax: 919-515-7591
Email: davidian@stat.ncsu.edu
Abstract: An ongoing research effort within the Center for Drug Evaluation and Research at the FDA has resulted in new guidelines that will require sponsors to show evidence of individual bioequivalence both of generic and innovator drugs and of innovator products subject to post-approval changes. Throughout the development of the new criteria, members of the FDA working group devoted to this effort made regular presentations to the Advisory Committee for Pharmaceutical Science (formerly the Generic Drugs Advisory Committee) on matters of rationale and implementation, and the issue was a matter of some debate. I served as the sole statistician on the Committee during this period. I will review the process leading to the new draft guidance, recount the impressions and comments of the members of the Committee, and provide my own perspective on the statistical issues involved.
2. Evaluation of Individual Bioequivalence: An Industry's Perspective
Chow, Shein-Chung, Covance, Inc.
Address: Executive Director, Biostatistics and Data Management Center for Scientific and Technical Services Covance Clinical and Periapproval Services, Inc. 210 Carnegie Center Princeton, New Jersey 08540-6233
Phone: 609-452-4457
Fax: 609-987-9048
Email: scchow@aol.com
Abstract: Individual bioequivalence as the requirement for approval of generic drug products and post-NDA-approval changes will be addressed with respect to average bioequivalence in terms of scientific merit and true necessity. Focus will be on the aggregate criterion suggested in the FDA draft guidance. Advantages and drawbacks of its corresponding statistical procedures and designs recommended in the draft guidance will be discussed with respect to their statistical properties, difficulty in application, interpretation, and the cost required for any potential gain of additional information. Other procedures based on different criteria for assessment of individual bioequivalence will also be discussed and compared to the FDA methods. Feasibility of the FDA draft guidance will be also discussed.
3. Uncertainty of Estimated Variances in the Determination of Individual Bioequivalence
Endrenyi, Laszlo, University of Toronto
Address: Department of Pharmacology Medical Sciences Building University of Toronto Toronto, Canada M5S, 1A8
Phone: 416-978-2728
Fax: 416-978-6395
Email: l.endrenyi@utoronto.ca
Abstract: Multiperiod crossover trials enable the estimation of intraindividual variances of the test and reference formulations (s2WT and s2WR). However, estimated variance are sensitive to single measurements and, especially, outliers. Moreover, the FDA Guidance suggests that difference (s2WT - s2WR) could be a basis for offering a reward to an improved test product. However, according to the recommended model, a large reward or penalty, could occur just by chance with high probability. This raises questions about the usefulness of the model for its implementation.
Discussant: Bolognese, James A. Merck Research Laboratories
Address: Merck Research Labs RY33-404 126 Lincoln Ave. Rahway, NJ 07065
Phone: 732-594-4412
Fax: 732-594-6075
Email: jim_bolognese@merck.com
List of speakers who are nonmembers: 1